Tsg101和液泡蛋白分选途径对于HIV-1出芽至关重要。

Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding.

作者信息

Garrus J E, von Schwedler U K, Pornillos O W, Morham S G, Zavitz K H, Wang H E, Wettstein D A, Stray K M, Côté M, Rich R L, Myszka D G, Sundquist W I

机构信息

Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.

出版信息

Cell. 2001 Oct 5;107(1):55-65. doi: 10.1016/s0092-8674(01)00506-2.

DOI:10.1016/s0092-8674(01)00506-2

PMID:11595185

Abstract

Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells. We now show that Tsg101 protein, which functions in vacuolar protein sorting (Vps), is required for HIV-1 budding. The UEV domain of Tsg101 binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein and also to ubiquitin. Depletion of cellular Tsg101 by small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of Tsg101. Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding. These observations suggest that retroviruses bud by appropriating cellular machinery normally used in the Vps pathway to form multivesicular bodies.

摘要

与其他包膜病毒一样，HIV-1利用细胞机制从受感染细胞中出芽。我们现在发现，参与液泡蛋白分选（Vps）的Tsg101蛋白是HIV-1出芽所必需的。Tsg101的UEV结构域与结构Gag蛋白p6结构域内的一个必需四肽（PTAP）基序结合，也与泛素结合。通过小干扰RNA耗尽细胞内的Tsg101会使HIV-1出芽在后期停滞，重新引入Tsg101可挽救出芽。抑制液泡蛋白分选的显性负性突变体Vps4蛋白也会使HIV-1和MLV出芽停滞。这些观察结果表明，逆转录病毒通过利用Vps途径中通常用于形成多泡体的细胞机制出芽。